Polypeptide growth factors are a class of natural biological mediators that regulate the proliferation, differentiation, motility and matrix synthesis of nearly all cell types. These properties, demonstrable in vitro, have led to the proposal that such factors play important roles in soft and hard tissue repair. Platelet-derived growth factor (PDGF) is a very well characterized example of such a polypeptide growth factor.
PDGF is a peptide hormone produced by blood platelets which influences the regulation of a broad array of biological systems including wound repair, arteriosclerosis, neoplasia, embryogenesis and bone marrow fibrosis. PDGF is a mitogen which is a substance which induces mitosis of cells and thus cellular proliferation. In wound repair, PDGF elicits both chemotaxis and mitogenic responses (i.e., induces mitosis) in fibroblasts, smooth muscle, glial cells, etc. Injury to the endothelium lining the vessel wall is believed to cause platelets to adhere to exposed connective tissue at the wound site, with the concomitant release of PDGF. The released PDGF is thought to chemotactically recruit many cell types including fibroblasts, monocytes, glial and smooth muscle to migrate in to the site of the wound. PDGF is also believed to stimulate DNA synthesis and proliferation of these cells thereby increasing their numbers of the site of the wound. Increased cellular proliferation thus leads to accelerated tissue regeneration and wound repair.
The mitogenic property of PDGF has been augmented by the addition of insulin-like growth factor-1 (IGF-1), Antoniades et al., U.S. Pat. No. 4,861,757 and transforming growth factor alpha (TGF-.alpha.), Antoniades et al., U.S. Pat. No. 4,874,746. Levenson et al. (1985) J. Biol. Chem 260:8056-63 showed that the synthetic glucocorticoid, dexamethasone, acts synergistically with cartilage-derived growth factor (CDGF) to enhance the stimulation of DNA synthesis in quiescent Swiss 3T3 cells, approximately doubling DNA synthesis while having a neutral effect when added with PDGF. In addition, they presented data showing that the simultaneous addition of dexamethasone to PDGF stimulated cultures had no effect on DNA synthesis over that observed with PDGF alone.